Tizanidine side effects: what 23,722 FDA adverse event reports show
Drug class
Central alpha-2-adrenergic agonist
Who reports
23,722 reports · 62% serious · 1,920 with death outcome · 75% female
Used for
Tizanidine Tablets, USP is a central alpha-2-adrenergic agonist indicated for the management of spasticity. Because of the short duration of therapeutic effect, treatment with Tizanidine Tablets, USP should be reserved for those daily activities and times when relief of spasticity is most important .
What it is
Tizanidine Tablets, USP (tizanidine hydrochloride) is a central alpha 2 -adrenergic agonist. Tizanidine HCl is a white to off-white, fine crystalline powder, which is odorless or with a faint characteristic odor. Tizanidine is slightly soluble in water and methanol; solubility in water decreases as the pH increases.
Boxed warning
None in the current label
Causality screen of the 40 strongest signals
What the badges mean
- Labeled (related wording) The label describes this effect under different wording (e.g. 'neutropenia' for 'neutrophil count decreased'). Treated as known.
- Reporting / coding artifact An administrative, monitoring or exposure term (product issue, off-label use, 'test normal', overdose...). Not a biological reaction; a high PRR here reflects how reports are coded.
- Lab value / disease marker A laboratory result, investigation or disease-activity marker (antibody positive, CRP abnormal, swollen joint count) not described in the label. These usually mirror the monitored disease or testing protocol rather than a drug effect; not screened further.
- Not in label — unassessed Not found in the label text, not an artifact pattern. This is a genuine candidate for a formal causality assessment (Bradford Hill / WHO-UMC); it has NOT had one here.
Strongest disproportionality signals
Flagged terms (PRR ≥ 2, χ² ≥ 4, n ≥ 10), ranked by PRR; infinite PRRs (no comparator reports) excluded. The EBGM column is a second, shrinkage-based estimate (MGPS) with its 5th percentile EB05 and the BCPNN IC025; a pair flagged by PRR alone is marked PRR-only and should be read as fragile. The strata column recomputes the PRR on serious reports only (and, for the 300 most-reported drugs, adjusted for age band), and flags pairs whose reports are unusually skewed by sex or come mostly from consumers. Each row also shows the PRR against the other drugs of the same FDA class, which removes most confounding by the condition being treated, and a calibrated p-value: on validation, known non-causes average an ROR of about 2, so significance is judged against that empirical null (✓ = p < 0.05 after calibration). 1,114 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Optic nerve operation | 14 | 1,108.8 503.4–2,442.1ROR 1,109.4 · calibrated p 5e-14 ✓ | 293.0 EB05 185.5 · IC025 +3.9 3/3 methods agree | Reporting / coding artifact | serious n=14 | not reported in cached trials |
| Failure to suspend medication | 19 | 89.5 55.8–143.4ROR 89.5 · calibrated p 1e-6 ✓ | 75.3 EB05 51.0 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | serious n=19 | not reported in cached trials |
| Perineal infection | 14 | 66.3 38.5–114.1ROR 66.3 · calibrated p 9e-6 ✓ | 57.1 EB05 36.2 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious n=14 | not reported in cached trials |
| Stiff person syndrome | 19 | 52.4 33.0–83.2ROR 52.4 · calibrated p 3e-5 ✓ | 47.3 EB05 32.0 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious n=19 | not reported in cached trials |
| Chronic kidney disease-mineral and bone disorder | 49 | 42.1 31.6–56.1ROR 42.2 · calibrated p 5e-5 ✓ | 39.7 EB05 31.2 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious n=49 | not reported in cached trials |
| Hyperparathyroidism secondary | 106 | 38.6 31.8–46.9ROR 38.8 · calibrated p 7e-5 ✓ | 36.8 EB05 31.3 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious n=106 | not reported in cached trials |
| Infected dermal cyst | 15 | 38.1 22.7–63.9ROR 38.1 · calibrated p 2e-4 ✓ | 35.1 EB05 22.6 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=14 | not reported in cached trials |
| Nephrogenic anaemia | 183 | 36.0 31.1–41.7ROR 36.3 · calibrated p 1e-4 ✓ | 34.5 EB05 30.5 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious n=182 | not reported in cached trials |
| Rebound acid hypersecretion | 120 | 36.0 30.0–43.1ROR 36.1 · calibrated p 1e-4 ✓ | 34.4 EB05 29.5 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious n=120 | not reported in cached trials |
| Suspected suicide | 139 | 26.5 22.4–31.4ROR 26.7 · calibrated p 5e-4 ✓ | 25.7 EB05 22.3 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious n=139 · 100% clinician | not reported in cached trials |
| Arteriovenous fistula | 14 | 25.8 15.2–44.0ROR 25.9 · calibrated p 0.001 ✓ | 24.3 EB05 15.3 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious n=14 | not reported in cached trials |
| Bone demineralisation | 18 | 15.2 9.6–24.3ROR 15.2 · calibrated p 0.010 ✓ | 14.3 EB05 9.1 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious n=13 | not reported in cached trials |
| End stage renal disease | 279 | 13.6 12.1–15.3ROR 13.7 · calibrated p 0.010 ✓ | 13.4 EB05 12.1 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious PRR 12.5 | not reported in cached trials |
| Chronic kidney disease | 1,115 | 13.0 12.3–13.8ROR 13.6 · calibrated p 0.010 ✓ | 12.8 EB05 12.2 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious PRR 12.2 | not reported in cached trials |
| Dry age-related macular degeneration | 16 | 12.9 7.9–21.2ROR 13.0 · calibrated p 0.018 ✓ | 11.7 EB05 7.0 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious n=16 | not reported in cached trials |
| Encephalopathy | 340 | 12.4 11.2–13.8ROR 12.6 · calibrated p 0.014 ✓ | 12.2 EB05 11.2 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious PRR 11.5 · 100% clinician | not reported in cached trials |
| Muscle spasticity | 170 | 12.3 10.6–14.3ROR 12.4 · calibrated p 0.016 ✓ | 12.0 EB05 10.6 · IC025 +3.3 3/3 methods agree | Labeled (related wording) related wording | serious PRR 10.1 | not reported in cached trials |
| Accidental death | 25 | 12.1 8.1–17.9ROR 12.1 · calibrated p 0.021 ✓ | 11.3 EB05 7.7 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious n=25 · 100% clinician | not reported in cached trials |
| B-lymphocyte count decreased | 18 | 12.0 7.5–19.0ROR 12.0 · calibrated p 0.023 ✓ | 10.8 EB05 6.7 · IC025 +2.4 3/3 methods agree | Lab value / disease marker | serious n=12 | not reported in cached trials |
| Gastrointestinal hypomotility | 29 | 11.6 8.1–16.8ROR 11.6 · calibrated p 0.023 ✓ | 10.9 EB05 7.7 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious n=27 | not reported in cached trials |
| Lumbar radiculopathy | 15 | 11.5 6.9–19.1ROR 11.5 · calibrated p 0.028 ✓ | 10.0 EB05 5.9 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious n=13 | not reported in cached trials |
| Progressive multiple sclerosis | 15 | 11.5 6.9–19.1ROR 11.5 · calibrated p 0.028 ✓ | 10.0 EB05 5.9 · IC025 +2.2 3/3 methods agree | Labeled (related wording) related wording | – | not reported in cached trials |
| Jc polyomavirus test positive | 14 | 10.6 6.3–18.0ROR 10.6 · calibrated p 0.037 ✓ | 9.0 EB05 5.3 · IC025 +2.1 3/3 methods agree | Lab value / disease marker | – | not reported in cached trials |
| Impaired gastric emptying | 150 | 10.5 9.0–12.3ROR 10.6 · calibrated p 0.028 ✓ | 10.3 EB05 8.9 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious PRR 10.3 · 86% consumer | not reported in cached trials |
| Peroneal nerve palsy | 63 | 9.9 7.7–12.7ROR 9.9 · calibrated p 0.036 ✓ | 9.5 EB05 7.6 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious n=45 | not reported in cached trials |
| Lumbar spinal stenosis | 29 | 8.8 6.1–12.7ROR 8.8 · calibrated p 0.056 | 8.0 EB05 5.7 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious n=28 | not reported in cached trials |
| Cervical spinal stenosis | 17 | 8.8 5.4–14.1ROR 8.8 · calibrated p 0.063 | 7.5 EB05 4.8 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious n=15 | not reported in cached trials |
| Drug screen negative | 17 | 8.6 5.3–13.8ROR 8.6 · calibrated p 0.067 | 7.3 EB05 4.7 · IC025 +2.0 3/3 methods agree | Reporting / coding artifact | – | not reported in cached trials |
| Paraparesis | 17 | 8.5 5.3–13.7ROR 8.5 · calibrated p 0.069 | 7.2 EB05 4.6 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious n=16 | not reported in cached trials |
| Intervertebral disc degeneration | 80 | 7.7 6.1–9.5ROR 7.7 · calibrated p 0.079 | 7.3 EB05 6.1 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious PRR 7.6 · 73% consumer | not reported in cached trials |
| Dermal cyst | 21 | 7.6 5.0–11.7ROR 7.6 · calibrated p 0.090 | 6.7 EB05 4.5 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious n=18 | not reported in cached trials |
| Bladder disorder | 85 | 7.6 6.1–9.4ROR 7.6 · calibrated p 0.080 | 7.3 EB05 6.1 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious n=43 | not reported in cached trials |
| Neurogenic bladder | 18 | 7.6 4.8–12.0ROR 7.6 · calibrated p 0.094 | 6.5 EB05 4.3 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious n=15 | not reported in cached trials |
| Wheelchair user | 36 | 7.2 5.2–10.0ROR 7.2 · calibrated p 0.100 | 6.6 EB05 5.0 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious n=30 · 100% consumer | not reported in cached trials |
| Nerve compression | 74 | 7.1 5.7–9.0ROR 7.2 · calibrated p 0.096 | 6.8 EB05 5.6 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 7.9 | not reported in cached trials |
| Infusion site bruising | 17 | 7.1 4.4–11.5ROR 7.1 · calibrated p 0.112 | 6.1 EB05 4.0 · IC025 +1.8 3/3 methods agree | Not in label — unassessed | serious n=15 | not reported in cached trials |
| Fibula fracture | 23 | 7.1 4.7–10.6ROR 7.1 · calibrated p 0.110 | 6.3 EB05 4.4 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious n=23 · ♀ 100% (drug 75%) | not reported in cached trials |
| Secondary progressive multiple sclerosis | 15 | 7.0 4.2–11.7ROR 7.0 · calibrated p 0.118 | 5.9 EB05 3.8 · IC025 +1.7 3/3 methods agree | Labeled (related wording) related wording | serious n=15 | not reported in cached trials |
| Multiple sclerosis relapse | 546 | 7.0 6.5–7.6ROR 7.2 · calibrated p 0.093 | 6.9 EB05 6.5 · IC025 +2.7 3/3 methods agree | Labeled (related wording) related wording | serious PRR 7.2 | not reported in cached trials |
| Spinal stenosis | 32 | 7.0 4.9–9.9ROR 7.0 · calibrated p 0.109 | 6.4 EB05 4.7 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious n=28 | not reported in cached trials |
Trial evidence (ClinicalTrials.gov)
✓ Trial adverse-event data found on ClinicalTrials.gov
Largest completed trials with posted results that list Tizanidine as a study intervention. The right-hand column of the signal table shows whether each FAERS term was also recorded in these trials, with a real denominator (0 of 40 signal terms matched).
- NCT03068897 — Ibuprofen Plus Metaxolone, Tizanidine, or Baclofen for Low Back Pain (N=320, PHASE4; 4 AE terms posted; arms: Metaxalone; Tizanidine; Baclofen; Placebo)
- NCT01839279 — A Study to Define the ECG Effects of Tizanidine Compared to Placebo and the Positive Control, Moxifloxacin, in (N=136, PHASE2; 19 AE terms posted; arms: Tizanidine; Initial Placebo and Crossover to Moxiflo; Initial Moxifloxacin and Crossover to Pl; Placebo and Moxifloxacin Groups Combined)
Caveats: trial populations, doses and follow-up differ from the reporting population; AE terms are sponsor-coded and matched here by wording; absence from a trial list means the term was not reported above the sponsor's frequency threshold, not that it cannot occur.
Most frequently reported reactions
By raw co-report count, regardless of disproportionality. Common terms here are often the illness itself or generic outcomes.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Fatigue (tiredness) | 1,742 | 2.0 1.9–2.1ROR 2.1 · calibrated p 0.978 | 2.0 EB05 1.9 · IC025 +0.9 | Labeled adverse reaction exact term | serious PRR 1.9 | NCT01839279: 13/72 (18.1%) on Tizanidine; 1/32 (3.1%) control |
| Pain | 1,646 | 2.4 2.3–2.5ROR 2.5 · calibrated p 0.826 | 2.4 EB05 2.3 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 2.3 | NCT01839279: 4/72 (5.6%) on Tizanidine; 2/32 (6.2%) control |
| Drug ineffective (drug did not work) | 1,612 | 1.1 1.0–1.1ROR 1.1 · calibrated p 0.365 | 1.1 EB05 1.0 · IC025 +0.0 | Reporting / coding artifact | serious PRR 1.2 | not reported in cached trials |
| Nausea | 1,611 | 1.8 1.7–1.9ROR 1.9 · calibrated p 0.868 | 1.8 EB05 1.7 · IC025 +0.8 | Not in label — unassessed | serious PRR 1.9 | NCT01839279: 9/72 (12.5%) on Tizanidine; 4/32 (12.5%) control |
| Headache | 1,344 | 1.9 1.8–2.0ROR 2.0 · calibrated p 0.918 | 1.9 EB05 1.8 · IC025 +0.8 | Not in label — unassessed | serious PRR 2.0 | NCT01839279: 10/72 (13.9%) on Tizanidine; 5/32 (15.6%) control |
| Fall | 1,338 | 3.6 3.4–3.8ROR 3.7 · calibrated p 0.434 | 3.6 EB05 3.4 · IC025 +1.7 3/3 methods agree | Not in label — unassessed | serious PRR 2.8 | not reported in cached trials |
| Diarrhoea (diarrhea) | 1,132 | 1.6 1.5–1.6ROR 1.6 · calibrated p 0.696 | 1.6 EB05 1.5 · IC025 +0.5 | Not in label — unassessed | serious PRR 1.4 | not reported in cached trials |
| Chronic kidney disease | 1,115 | 13.0 12.3–13.8ROR 13.6 · calibrated p 0.010 ✓ | 12.8 EB05 12.2 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious PRR 12.2 | not reported in cached trials |
| Dizziness | 1,023 | 1.8 1.7–1.9ROR 1.9 · calibrated p 0.862 | 1.8 EB05 1.7 · IC025 +0.8 | Labeled adverse reaction exact term | serious PRR 1.8 | NCT03068897: 2/80 (2.5%) on Tizanidine |
| Off label use (used outside approved label) | 1,022 | 1.0 1.0–1.1ROR 1.0 · calibrated p 0.335 | 1.0 EB05 1.0 · IC025 -0.0 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | serious PRR 1.1 | not reported in cached trials |
| Vomiting | 846 | 1.6 1.5–1.7ROR 1.6 · calibrated p 0.718 | 1.6 EB05 1.5 · IC025 +0.6 | Labeled adverse reaction exact term | serious PRR 1.6 | not reported in cached trials |
| Arthralgia (joint pain) | 845 | 1.8 1.7–1.9ROR 1.8 · calibrated p 0.850 | 1.8 EB05 1.7 · IC025 +0.7 | Labeled adverse reaction exact term | serious PRR 1.9 | not reported in cached trials |
| Acute kidney injury (sudden kidney damage) | 819 | 4.8 4.5–5.1ROR 4.9 · calibrated p 0.245 | 4.7 EB05 4.5 · IC025 +2.1 3/3 methods agree | Labeled (related wording) related wording | serious PRR 4.5 | not reported in cached trials |
| Anxiety | 801 | 2.5 2.3–2.7ROR 2.5 · calibrated p 0.797 | 2.5 EB05 2.3 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 2.7 | not reported in cached trials |
| Asthenia (weakness) | 799 | 1.9 1.8–2.0ROR 1.9 · calibrated p 0.894 | 1.9 EB05 1.8 · IC025 +0.8 | Labeled adverse reaction exact term | serious PRR 1.8 | not reported in cached trials |
Unlabeled candidate signals
These flagged terms were not found in the FDA label text and do not match an artifact pattern. They are the pairs that would merit a structured assessment (temporality, dose-response, biological plausibility, consistency across databases, trial or cohort evidence). The screen has not done that; string-matching misses label wording, and a strong PRR can still be stimulated reporting, co-medication, or the disease itself.
- Chronic kidney disease-mineral and bone disorder — n=49, PRR 42.1
- Hyperparathyroidism secondary — n=106, PRR 38.6
- Nephrogenic anaemia — n=183, PRR 36.0
- Rebound acid hypersecretion — n=120, PRR 36.0
- Suspected suicide — n=139, PRR 26.5
- End stage renal disease — n=279, PRR 13.6
- Chronic kidney disease — n=1,115, PRR 13.0
- Encephalopathy — n=340, PRR 12.4
- Accidental death — n=25, PRR 12.1
- Gastrointestinal hypomotility — n=29, PRR 11.6
✓ A hand-written Bradford Hill causality assessment exists for this drug: Tizanidine ↔ Hypotension.
Want to assess one of these properly? The runbook describes the Bradford Hill / trial-evidence workflow used on the assessment page, and handoff_top1000_signals.csv lists the strongest unassessed pairs across all drugs.
Common questions
What are the most reported side effects of Tizanidine?
In FDA FAERS, the most frequently co-reported reaction terms for Tizanidine are fatigue, pain, nausea, headache, fall, diarrhoea. These are report counts, not rates: FAERS has no denominator, reporting is voluntary and uneven, and a term can be reported because of the illness being treated rather than the drug.
Does Tizanidine have an FDA boxed warning?
No. The FDA label retrieved for Tizanidine has no boxed warning; see the label's Warnings and Precautions for the recognised risks.
Do FAERS signals prove that Tizanidine causes these side effects?
No. A disproportionality signal (PRR, ROR) means a reaction is reported more often with this drug than with others in the database. That can reflect a real effect, but also the disease being treated, stimulated reporting after news or litigation, co-medications, or how reports are coded. Causality needs temporality, dose-response, biological plausibility, consistency across data sources and, ideally, trial or cohort evidence. This page screens each term against the FDA label and ClinicalTrials.gov results; it does not establish causation.
Sources & methods
- FDA label via openFDA (set ID 03fa03a6-fd05-4f17-872a-3c123330935d, effective 20231109; matched on
openfda.generic_name.exact:"TIZANIDINE") - Bayesian shrinkage measures computed offline over all 1,317,300 cached pairs: BCPNN information component (IC, with Norén closed-form IC025) and MGPS empirical-Bayes geometric mean (EBGM, EB05) with a two-component gamma prior fitted by maximum marginal likelihood (α₁=0.57, β₁=0.02, α₂=1.42, β₂=0.70, w=0.17); unstratified
- FAERS pair statistics from the OpenPV build of 2026-09-14 (openFDA
count=aggregation, fieldpatient.drug.openfda.generic_name.exact, 1,154 reaction terms, min 3 co-reports); PRR/ROR with 95% CI, chi-square with Yates correction - Serious-only and stratified counts (serious:1, patient.patientsex, primarysource.qualification) from openFDA count queries; serious-only PRR uses the drug serious report total and the term global serious total (N_serious=11,882,979); strata shown only when n ≥ 20
- Seriousness and sex counts from openFDA
count=serious,patient.patientsex,seriousnessdeath - ClinicalTrials.gov API v2 (query
TIZANIDINE, results-bearing studies sorted by enrollment)
Page generated 2026-10-14. Label and PubChem text are retrieved automatically and may lag the current label; always check the current prescribing information. OpenPV is a beta research tool of the Open Source Medicine Foundation.